p16-positive lymph node metastases from cutaneous head and neck squamous cell carcinoma: No association with high-risk human papillomavirus or prognosis and implications for the workup of the unknown primary

Cancer. 2016 Apr 15;122(8):1201-8. doi: 10.1002/cncr.29901. Epub 2016 Feb 16.

Abstract

Background: The incidence of p16 overexpression and the role of human papillomavirus (HPV) in cutaneous head and neck squamous cell carcinoma (cHNSCC) are unclear.

Methods: One hundred forty-three patients with cHNSCC lymph node metastases involving the parotid gland were evaluated for p16 expression by immunohistochemistry. The detection of 18 high-risk HPV subtypes was performed with HPV RNA in situ hybridization for a subset of 59 patients. The results were correlated with clinicopathological features and outcomes.

Results: The median follow-up time was 5.3 years. No differences were observed in clinicopathological factors with respect to the p16 status. p16 was positive, weak, and negative in 45 (31%), 21 (15%), and 77 cases (54%), respectively. No high-risk HPV subtypes were identified, regardless of the p16 status. The p16 status was not prognostic for overall (hazard ratio, 1.08; 95% confidence interval [CI], 0.85-1.36; P = .528), cancer-specific (hazard ratio, 1.12; 95% CI, 0.77-1.64; P = .542), or progression-free survival (hazard ratio, 1.03; 95% CI, 0.83-1.29; P = .783). Distant metastasis-free survival, freedom from locoregional failure, and freedom from local failure were also not significantly associated with the p16 status.

Conclusions: p16 positivity is common but not prognostic in cHNSCC lymph node metastases. High-risk HPV subtypes are not associated with p16 positivity and do not appear to play a role in this disease. HPV testing, in addition to the p16 status in the unknown primary setting, may provide additional information for determining a putative primary site.

Keywords: head and neck cancer; human p16 protein; papillomavirus infections; skin neoplasms; squamous cell neoplasms; unknown primary neoplasms.

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / secondary
  • Carcinoma, Squamous Cell / virology*
  • Cohort Studies
  • Cyclin-Dependent Kinase Inhibitor p16
  • Databases, Factual
  • Female
  • Follow-Up Studies
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / secondary
  • Head and Neck Neoplasms / virology*
  • Human papillomavirus 16 / genetics
  • Humans
  • Kaplan-Meier Estimate
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Neoplasms, Unknown Primary / genetics
  • Neoplasms, Unknown Primary / mortality
  • Neoplasms, Unknown Primary / pathology*
  • Papillomavirus Infections / pathology*
  • Papillomavirus Infections / virology
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Assessment
  • Sex Factors
  • Skin Neoplasms / mortality
  • Skin Neoplasms / secondary
  • Skin Neoplasms / virology*
  • Statistics, Nonparametric
  • Survival Analysis
  • Time Factors

Substances

  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Neoplasm Proteins